title: Regulation of corticotropin-releasing factor and urocortin 2/3 mRNA by leptin in hypothalamic N39 cells.
abstract: Corticotropin-releasing factor (CRF) activates the pituitary-adrenal axis during stress, and shows anorectic effects via CRF type 1 receptors in the hypothalamus. Both urocortin (Ucn) 2 and Ucn3 also act as anorectic neuropeptides via CRF type 2 receptors. Leptin, a product of the obesity gene secreted mainly from adipose tissue, reduces food intake and increases energy expenditure. A possible interaction between leptin and CRF/Ucns has been suggested, as leptin can regulate expression and activation of CRF and Ucns in the hypothalamus. This study aimed to explore the possible function of leptin in the hypothalamus, and its effects in regulating CRF and Ucns. The study identified mRNA expression of the leptin receptor (Ob-R) and its subtypes, CRF, and Ucn2/3 in mouse hypothalamic N39 cells. Leptin stimulated signal transducer and activators of transcription type 3 (STAT3) phosphorylation, directly increased the mRNA levels of both CRF and Ucn2/3 in hypothalamic cells, and increased Ob-Rb mRNA levels. A Janus kinase inhibitor inhibited the leptin-mediated increase in STAT3 phosphorylation, and then the increases in CRF and Ucn2/3 mRNA levels. Leptin may contribute to a stress response or anorectic effect via the regulation of CRF and Ucn2/3 in the hypothalamus.
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kageyama
authors.forename: Kanako
authors.initials: K
authors.lastname: Akimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Watanuki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suda
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
mesh_terms: D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054832:Urocortins / Q000235:genetics* / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D020738:Leptin; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D054832:Urocortins; C515447:leptin receptor, mouse; C518358:urocortin 2, mouse; C549823:urocortin 3 protein, mouse; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D053612:Janus Kinases
keywords: Corticotropin-releasing factor; Hypothalamus; Leptin; Stress; Urocortin